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Even though the international combat against Neglected Tropical Diseases such as schistosomiasis or soil-transmitted helminthiases depends on reliable therapeutics, anthelminthic pharmacovigilance has been neglected on many national African drug markets. Therefore, quality and composition of 88 different batches of Albendazole, Mebendazole and Praziquantel locally collected from randomly selected facilities in Western Burkina Faso, Southeast Côte d’Ivoire, Southwest Ghana and Northwest Tanzania were analysed.
Visual examination of both packaging and samples was performed according to the WHO ‘Be Aware’ tool. Products were then screened with the GPHF Minilab, consisting of tests of mass uniformity, disintegration times and thin-layer chromatography (TLC). Confirmatory tests were performed according to international pharmacopoeiae, applying assays for dissolution profiles and high-performance liquid chromatography (HPLC).
Despite minor irregularities, appearance of the products did not hint at falsified medicines. However, 19.6 % of the brands collected in Ghana and Tanzania were not officially licensed for sale. Mass uniformity was confirmed in 53 out of 58 brands of tablets. 41 out of 56 products passed disintegration times; 10 out of the 15 failing products did not disintegrate at all.
TLC results did not reveal any falsifications or pronounced dosing errors. HPLC findings confirmed the TLC results despite shifted specification limits: ten of the 83 tested batches contained less than 90 %, none more than 110 % label claim. However, no more than 46.3 % (31 / 67) of the tablet batches assayed passed the respective criteria for dissolution.
In the four study countries, no falsified anthelminthic medicine was encountered. The active pharmaceutical ingredient was not found to either exceed or distinctively fall below specification limits. Galenic characteristics as most critical criteria however, especially dissolution profiles, revealed substantial deficits.
The present study investigates the infection rates of parasites, morbidity, and the living conditions of street children and orphans in Mwanza city, northern Tanzania. A high percentage of orphans and street children in Mwanza city is infected with one or more parasites. A significantly higher rate of infections with S. mansoni in street children as compared with orphans could be observed. The prevalence of S. mansoni determined by POC CCA test was 65.9% for orphans and 94.5% for street children. 19.2% of the orphans tested positive for S. mansoni in Kato Katz. Of the street children, 77.1% showed positive test results in Kato-Katz. Only 1.3% of the orphans stated in the questionnaire that they use the lake to wash, whereas 91.1% of the street children named the lake as at least one of their options for washing. Protozoal infections used as a marker for hygiene were at a comparable level for both groups. Microscopy showed positive results for G. intestinalis in 8.2% and for E. histolytica/dispar in 23% of orphans and 8.1% for G. intestinalis, and 23.8% for E. histolytica/dispar in street children. Through ultrasonography, we observed no signs of severe PPF and only a few mild PPF patterns. Most street children use the lake to wash and often do not have access to adequate sanitation. However, everyone in the study group indicated having access to safe drinking water. Overall, we found the general hygienic conditions for both groups to be inadequate. With the help of simple public health measures, like improve sanitation and regular mass drug administration, the overall situation would likely be considerably improved.
The StrongPaed study in the paediatric ward of a referral hospital in Mwanza in the lake region of Tanzania showed the prevalence of S. stercoralis, G. lamblia, E. histolytica and E. dispar as well as of other intestinal parasites with various diagnostic methods.
The prevalence of S. stercoralis was 2-10 % depending on the diagnostic methods used. There were no symptomatic infections but only carriage of the nematode. The positive results differed greatly depending on the performed diagnostic methods. None of the diagnostics showed satisfying results, neither in sensitivity and specificity nor in feasibility for this population in an endemic region in sub-Saharan Africa. PCR and microscopy were limited by the low amount of examined stool samples and by the resulting lack of sensitivity. Stool cultures were limited by time-consuming procedures and mainly by the problem of differentiation from hookworm and the resulting lack of specificity. ELISA was limited by the need of blood samples and also by poor specificity in the ELISA used.
The prevalence of G. lamblia was high, but mostly only carriage and not symptomatic infections was seen. No E. histolytica was detected, but 8.5 % samples were positive for E. dispar. Among the performed diagnostics, the rapid test showed sufficient results. It showed better sensitivity than microscopy and is cheaper and more feasible than PCR. Differentiation between E. histolytica and E. dispar was only possible with qPCR performed in Germany.
More children were positive for intestinal parasites from rural than from urban areas. The profession of the parents working as farmers was a risk factor for intestinal parasitic infections. Hygienic living conditions such as access to tap water and flush toilets at home were preventive for intestinal parasitic infections in children.
Objectives
Dengue virus (DENV) detection by polymerase chain reaction (PCR) facilitates diagnosis of dengue fever, which is the most frequent arboviral disease globally. Two studies were performed in countries with high dengue incidence, to assess the diagnostic performance of different PCR techniques.
Methods/Results
Two hundred and seventy‐nine acute phase blood samples from febrile patients were analyzed for DENV by the RealStar Dengue RT‐PCR kit (Altona Diagnostics) as gold standard in comparison with the Tropical Fever Core multiplex PCR (Fast Track Diagnostics). In total, 102 samples collected in Savannakhet Province (Lao PDR, Southeast Asia) in 2013 and 35 samples from Valledupar (Colombia, South America) tested positive for DENV by RealStar RT‐PCR. In comparison, the Tropical Fever Core multiplex PCR detected 65.0% (65/102) and 68.6% (24/35) of these samples as positive for DENV in Savannakhet and Valledupar, respectively. Diagnostic sensitivity of the multiplex PCR strongly correlated with viral load. A subset of DENV PCR‐confirmed samples was additionally tested by BNITM in house Dengue Type RT‐PCR in comparison with two commercial test kits (RealStar Dengue Type RT‐PCR [Altona Diagnostics], Dengue differentiation PCR [Fast Track Diagnostics]). The leading dengue serotype in Savannakhet was DENV‐3 (58% [29/50]), while DENV‐1 (53.8% [14/26]) was the predominant serotype found in samples collected in Valledupar by BNITM‐type PCR. However, three DENV serotypes were circulating in Valledupar and in Savannakhet. In 2015, additional studies found predominantly DENV‐4 (71% [12/17]) in Savannakhet.
Conclusions
Both studies emphasized that routine diagnostics in both regions will benefit from an expanded use of highly sensitive pan‐dengue PCRs.
Objectives
Specific serological tests are mandatory for reliable SARS‐CoV‐2 diagnostics and seroprevalence studies. Here, we assess the specificities of four commercially available SARS‐CoV‐2 IgG ELISAs in serum/plasma panels originating from Africa, South America, and Europe.
Methods
882 serum/plasma samples collected from symptom‐free donors before the COVID‐19 pandemic in three African countries (Ghana, Madagascar, Nigeria), Colombia, and Germany were analysed with three nucleocapsid‐based ELISAs (Euroimmun Anti‐SARS‐CoV‐2‐NCP IgG, EDI™ Novel Coronavirus COVID‐19 IgG, Mikrogen recomWell SARS‐CoV‐2 IgG), one spike/S1‐based ELISA (Euroimmun Anti‐SARS‐CoV‐2 IgG), and in‐house common cold CoV ELISAs.
Results
High specificity was confirmed for all SARS‐CoV‐2 IgG ELISAs for Madagascan (93.4–99.4%), Colombian (97.8–100.0%), and German (95.9–100.0%) samples. In contrast, specificity was much lower for the Ghanaian and Nigerian serum panels (Ghana: NCP‐based assays 77.7–89.7%, spike/S1‐based assay 94.3%; Nigeria: NCP‐based assays 39.3–82.7%, spike/S1‐based assay 90.7%). 15 of 600 African sera were concordantly classified as positive in both the NCP‐based and the spike/S1‐based Euroimmun ELISA, but did not inhibit spike/ACE2 binding in a surrogate virus neutralisation test. IgG antibodies elicited by previous infections with common cold CoVs were found in all sample panels, including those from Madagascar, Colombia, and Germany and thus do not inevitably hamper assay specificity. Nevertheless, high levels of IgG antibodies interacting with OC43 NCP were found in all 15 SARS‐CoV‐2 NCP/spike/S1 ELISA positive sera.
Conclusions
Depending on the chosen antigen and assay protocol, SARS‐CoV‐2 IgG ELISA specificity may be significantly reduced in certain populations probably due to interference of immune responses to endemic pathogens like other viruses or parasites.
S. stercoralis is a helminthic parasite which is common in tropical and subtropical regions. It causes a persistent but often inapparent infection in humans. In the state of a protracted immunosuppression this parasite can cause a life-threatening hyperinfection syndrome. Most often the hyperinfection syndrome was found after prolonged high dose corticosteroid treatment. In HIV-infected individuals high dose corticosteroids are used for the treatment of the immune reconstitution inflammatory syndrome (IRIS) or as adjunct treatment in the treatment of meningeal or pericardial tuberculosis. Case reports from Tanzania demonstrate that Strongyloidiasis is prevalent not only in coastal regions but also in the Lake province of Tanzania. However, data on the local prevalence of S. stercoralis infection based on sensitive techniques are scanty, especially in HIV-infected individuals.
The main objective of this study is to provide data on the prevalence of S. stercoralis infections in the adult HIV-infected population attending the Bugando Medical Centre for medical care. Specific objectives of the study are the comparison of the sensitivities and specificities of five different methods in detecting S. stercoralis. Four methods to detect S. stercoralis larvae used stool samples; one method to detect S. stercoralis antibodies required blood samples. The study used the Agar-plate-culture-technique and a modified Harada-Mori-culture-technique for the direct detection of helminthic larvae in the collected faecal samples. In addition, a recently described PCR-assay from faecal specimens and an ELISA for S. stercoralis antibodies have been applied. The Faecal Parasite Concentrator (FPC) stool concentration technique was used for the differential diagnosis of other intestinal helminthic parasites. The results of the study may influence the current treatment guidelines for HIV-infected patients in case that a relevant prevalence of S. stercoralis infection is found. Then, prior to a prolonged iatrogenic immunosuppression -like the high dose corticosteroid treatment for IRIS- a prophylactic anthelminthic treatment capable to eradicate a S. stercoralis infection could be recommendable. The prevalence of a current S. stercoralis infection using the PCR as a gold standard was 5.4%. The Agar plate method showed positive results in 19 out of 278 cases (6.1%), the modified Harada Mori technique in 13 of 278 (4.7%) cases. With PCR as gold standard the sensitivity of the agar plate method was 60%, the positive predictive value 47.4%, the specificity 96.2% and the negative predictive value 97.7 %. The sensitivity of the Harada Mori technique was 36.4%, the positive predictive value 30.7% with a specificity of 96.4% and negative predictive value 97.1%. The modified Harada Mori technique allowed in principal the morphological identification of nematode larvae. Microscopic analysis showed a specificity of 100% and a sensitivity of 46.7%. Antibodies were detected in 45 of 278 cases 16.2% by ELISA, with a sensitivity of 92.9% and a specificity of 87.8%. The findings of this study show that none of the diagnostic tests can be implemented as a routine diagnostic procedure to diagnose a current infection. This leads to the conclusion that it is high time to consider the provision of a prophylactic treatment within patients who are either HIV positive patients who could develop an IRIS after receiving ART, patients with a HTLV-1 infection and the growing number of patients under iatrogenic immunosuppression for various reasons.
Bacterial distribution and antimicrobial drug resistance were monitored in patients with bacterial bloodstream infections in rural hospitals in Ghana. In 2001-2002 and in 2009, Salmonella enterica serovar Typhi was the most prevalent pathogen. Although most S. enterica serovar Typhi isolates were chloramphenicol resistant, all isolates tested were susceptible to ciprofloxacin.
Background
The World Health Organization (WHO) has recommended guidelines for a HIV drug resistance (HIVDR) survey for resource-limited countries. Eligibility criteria for patients include age below 25 years in order to focus on the prevalence of transmitted HIVDR (tHIVDR) in newly-infected individuals. Most of the participating sites across Africa have so far reported tHIVDR prevalences of below 5%. In this study we investigated whether the rate of HIVDR in patients <25 years is representative for HIVDR in the rest of the therapy-naïve population.
Methods and Findings
HIVDR was determined in 88 sequentially enrolled ART-naïve patients from Mwanza, Tanzania (mean age 35.4 years). Twenty patients were aged <25 years and 68 patients were aged 25–63 years. The frequency of HIVDR in the study population was 14.8% (95%; CI 0.072–0.223) and independent of NVP-resistance induced by prevention of mother-to-child transmission programs. Patients >25 years had a significantly higher HIVDR frequency than younger patients (19.1%; 95% CI 0.095–0.28) versus 0%, P = 0.0344). In 2 out of the 16 patients with HIVDR we found traces of antiretrovirals (ARVs) in plasma.
Conclusions
ART-naïve patients aged over 25 years exhibited significantly higher HIVDR than younger patients. Detection of traces of ARVs in individuals with HIVDR suggests that besides transmission, undisclosed misuse of ARVs may constitute a significant factor in the generation of the observed high HIVDR rate. The current WHO tHIVDR survey that is solely focused on the transmission of HIVDR and that excludes patients over 25 years of age may therefore result in substantial underestimation of the prevalence of HIVDR in the therapy-naïve population. Similar studies should be performed also in other areas to test whether the so far reported optimistic picture of low HIVDR prevalence in young individuals is really representative for the rest of the ART-naïve HIV-infected population.
Background
Epithelial surfaces such as the gastrointestinal mucosa depend on expression of antimicrobial peptides like cathelicidin for immune defence against pathogens. The mechanisms behind mucosal cathelicidin regulation are incompletely understood.
Methods
Cathelicidin expression was analysed in duodenal, antral and corpus/fundic mucosal biopsies from African and German patients. Additionally, cathelicidin expression was correlated with Helicobacter pylori (HP) infection and the inflammatory status of the mucosa.
Results
High cathelicidin transcript abundance was detected in duodenal biopsies from African subjects. On the contrary, cathelicidin mRNA expression was either undetectable or very low in tissue specimens from German patients. Also, in the antrum and corpus/fundus regions of the stomach significantly higher cathelicidin transcript levels were measured in Tanzanian compared to German patients. In gastric biopsies from African patients cathelicidin expression was increased in HP positive compared to HP negative subjects. Additionally, the inflammatory status measured by IL-8 expression correlated well with the HP infection status.
Conclusions
A higher duodenal and gastric cathelicidin expression in African (compared with European) individuals may be due to upregulation by antigenic stimulation and may confer a higher resistance against enteric infections.
Background
Chronic thromboembolic pulmonary hypertension (CTEPH) is a long-term complication following an acute pulmonary embolism (PE). It is frequently diagnosed at advanced stages which is concerning as delayed treatment has important implications for favourable clinical outcome. Performing a follow-up examination of patients diagnosed with acute PE regardless of persisting symptoms and using all available technical procedures would be both cost-intensive and possibly ineffective. Focusing diagnostic procedures therefore on only symptomatic patients may be a practical approach for detecting relevant CTEPH.
This study aimed to evaluate if a follow-up program for patients with acute PE based on telephone monitoring of symptoms and further examination of only symptomatic patients could detect CTEPH. In addition, we investigated the role of cardiopulmonary exercise testing (CPET) as a diagnostic tool.
Methods
In a prospective cohort study all consecutive patients with newly diagnosed PE (n=170, 76 males, 94 females within 26 months) were recruited according to the inclusion and exclusion criteria. Patients were contacted via telephone and asked to answer standardized questions relating to symptoms. At the time of the final analysis 130 patients had been contacted. Symptomatic patients underwent a structured evaluation with echocardiography, CPET and complete work-up for CTEPH.
Results
37.7%, 25.5% and 29.3% of the patients reported symptoms after three, six, and twelve months respectively. Subsequent clinical evaluation of these symptomatic patients saw 20.4%, 11.5% and 18.8% of patients at the respective three, six and twelve months time points having an echocardiography suggesting pulmonary hypertension (PH). CTEPH with pathological imaging and a mean pulmonary artery pressure (mPAP) ≥ 25 mm Hg at rest was confirmed in eight subjects. Three subjects with mismatch perfusion defects showed an exercise induced increase of PAP without increasing pulmonary artery occlusion pressure (PAOP). Two subjects with pulmonary hypertension at rest and one with an exercise induced increase of mPAP with normal PAOP showed perfusion defects without echocardiographic signs of PH but a suspicious CPET.
Conclusion
A follow-up program based on telephone monitoring of symptoms and further structured evaluation of symptomatic subjects can detect patients with CTEPH. CPET may serve as a complementary diagnostic tool.